Saito Yuichi, Nishi Takeshi, Wakabayashi Shinichi, Ohno Yuji, Kitahara Hideki, Ariyoshi Noritaka, Kobayashi Yoshio
Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.
Division of Cardiovascular Medicine, Stanford University School of Medicine and Stanford Cardiovascular Institute.
J Atheroscler Thromb. 2022 Jul 1;29(7):1031-1039. doi: 10.5551/jat.63035. Epub 2021 Jul 8.
High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear.
Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR.
A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles.
Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.
高血小板反应性（HPR）与冠心病患者血栓形成事件风险增加相关。最近开发的ABCD-GENE评分确定了五个与HPR相关的临床和遗传因素（年龄、体重指数、慢性肾病、糖尿病和CYP2C19功能缺失等位基因），但每个因素不同阶段的意义尚不清楚。
汇总四项前瞻性研究，其中使用VerifyNow检测法测定氯吡格雷和普拉格雷治疗后的血小板反应性；同时对CYP2C19进行基因分型。将ABCD-GENE评分的每个组成部分分为三个亚类。VerifyNow P2Y12反应单位＞208被定义为HPR。
共纳入184例患者，其中111例（60%）和51例（28%）分别在使用氯吡格雷和普拉格雷治疗后出现HPR。慢性肾病对氯吡格雷和普拉格雷治疗后的HPR均有影响，而糖尿病对普拉格雷治疗患者的影响更为明显。虽然CYP2C19功能缺失等位基因数量与氯吡格雷治疗后发生HPR的可能性明显相关，但在携带更多CYP2C19功能缺失等位基因的患者中，普拉格雷治疗后的P2Y12反应单位也显著且逐步升高。
临床和遗传因素对冠心病患者使用氯吡格雷和普拉格雷时的P2Y12抑制剂反应性有不同影响。这些因素的严重程度对HPR的影响也有所不同。
